The precise mechanism of the hypospermatogenesis associated with varicocele has remained uncertain, although there have been a number of speculations on the etiology of the associated infertility. The altered spermatogenesis has been attributed to the reflux of toxic metabolites from either adrenal or renal origin, disturbed hormone status, spermatic venous hypertension, testicular hypoxia secondary to stasis, and abnormal temperature regulation. However, the biochemical changes of the testicular tissue with varicocele have been only partially explored. This overview includes the available information on the biochemical change in the testes associated with varicocele as well as the introduction of basic biochemical aspects on the testes, which may give new insights into the possible pathophysiological mechanism of male infertility.